An outbred colony of rats designated "BB" contains numerous members which develop insulin dependent, ketosis prone diabetes at a young age. Over 99 percent of animals which become glycosuric develop ketoacidosis and die unless treated with insulin, and histological examination of the pancreas shows insulitis. Rat family studies show that susceptibility to BB diabetes is genetically determined. Because these characteristics resemble juvenile type insulin dependent diabetes in man, this model will be studied in detail. Emphasis will be placed on determining whether or not susceptibility to BB rat diabetes segregates with the major histocompatibility complex in a manner analogous to the linkage of juvenile type diabetes to the HLA complex in some families. (cf. the association of diabetes and HLA in many populations). Inbred lines of rats will be constructed in order to study the BB diabetes gene (or genes) on inbred backgrounds from well characterized strains. The effect of other genes on the expression of the diabetes gene will then be examined. Based on preliminary positive evidence, some investigations designed to prevent BB diabetes progression after diagnosis will be pursued.